P e d i a t r i c P ro c e d u r a l S e d a t i o n an d

Analgesia
Garrett S. Pacheco,

MD,

Angelique Ferayorni,

DO*

KEYWORDS
 Sedation  Analgesia  Pediatrics  Procedures
KEY POINTS
 Analgesia and sedation are often underused in pediatrics.
 Review of available treatment agents for pain and sedation.
 Understand that a childs developmental level can affect pain assessment.
 Review of adverse reactions to commonly used sedation and analgesia.

Sedation and analgesia have historically been criticized for being poorly delivered in
the pediatric population. In 2001, the American Academy of Pediatrics Task Force
on Pain in Infants, Children, and Adolescents identified barriers in the treatment of
pain including the myth that children do not feel pain the way adults do, the lack of
pain assessment in pediatrics, and lack of knowledge of pain treatment.1 Since its
release, there have been encouraging improvements in the recognition and treatment
of pain. For example, a recent clinical report has identified several studies that have
shown an increase in opiate use in children with fractures as an example of the trend
to address pediatric pain adequately.2
The practice of pediatric sedation and pain control has significantly evolved with
new pharmacologic agents, painless interventions, improved continuous monitoring,
and safety protocols. Despite such advances, clinicians can still be reluctant to use
sedation and analgesia with pediatric patients.3 The emergency physician should
have a firm understanding of the available modalities for treating pain and must be
able to provide sedation for painful or anxiety-provoking procedures in the emergency
department. This article focuses on various delivery methods for procedural sedation
and analgesia (PSA) as well as future trends in the field.

Disclosures: None.
Department of Pediatrics and Emergency Medicine, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724-5057, USA
* Corresponding author.
E-mail address: aferayorni@gmail.com
Emerg Med Clin N Am 31 (2013) 831852
http://dx.doi.org/10.1016/j.emc.2013.04.002
0733-8627/13/$ see front matter 2013 Elsevier Inc. All rights reserved.

emed.theclinics.com

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SEDATION CONTINUUM

Although a patient who is conscious but cooperative is ideal, physicians often need a
deeply sedated patient who is immobile to achieve procedural success. In 1992, the
Committee on Drugs of the American Academy of Pediatrics (AAP) released its original
Guidelines for Monitoring and Management of Pediatric Patient During and After Sedation for Diagnostic and Therapeutic Procedures. These guidelines define conscious
sedation as a stage of sedation that allows an appropriate response by the patient
to physical stimulation or verbal command.4 The intention of the Committee was for
conscious sedation to be viewed as a minimal state of sedation; however, this concept
was ambiguous. In 2002, an addendum was made and the terms were adopted by The
Joint Commission.
Conscious sedation was redefined as being moderate sedation and analgesia. At
this stage of sedation the patient should have a depressed level of consciousness
during which the patient responds purposefully to verbal commands, either alone or
accompanied by light tactile stimulation. At the same time, a lesser stage of sedation
was acknowledged, termed minimal sedation anxiolysis.5 A patient who approaches
deep sedation may have suppressed or lost protective airway reflexes or ventilatory
compromise. They are not easily aroused. General anesthesia occurs when the patient
is often unarousable, has often lost protective airway reflexes, and may have impaired
ventilation and cardiovascular function. Dissociative sedation does not fit in one of
these categories. The patient experiences amnesia, analgesia, and sedation. Patients
are minimally responsive to tactile stimulation, but able to protect their airways. The
depth of sedation should vary depending on each clinical situation. These levels of
sedation represent a continuum (Fig. 1). The physician should be comfortable supporting or reversing the patient should they go beyond the intended sedation level.
UNDERSTANDING A CHILDS DEVELOPMENTAL LEVEL

To reduce the incidence of pain and anxiety that accompanies a diagnostic or therapeutic procedure, nonpharmacologic interventions should be pursued. Nonpharmacologic measures include cognitive and behavioral approaches. When sedation is
desired and a nonpharmacologic tool is selected, it is important to keep in mind the
developmental and cognitive ability of the patient. Reasoning is rarely useful for children between the ages of 2 and 7 years. However, verbal preparation that is developmentally appropriate can start at the age of 3 years old to help reduce anxiety. Children
8 years old and older benefit from an explanation for the required procedure. Preparation and distraction are important aspects of the preprocedural checklist. Child life

Fig. 1. Sedation level continuum.

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has shown an increasing role in this portion of the preparation.6 Child life specialists
aid in the planning and rehearsing of coping mechanisms for the child and establish
therapeutic relationships with children and parents to support family involvement in
each childs care before a procedure. Play therapy can facilitate understanding and
distraction. Music, video, and imagery are tools to aid in preparation and distraction.
Distraction tools include movies, toy robots, dolls, virtual reality goggles, music, bubbles, short stories, games, and iPads or digital tablets. Medical supplies, such as playing with syringes, can also be used to prepare the patient and reduce the fear and
anxiety of unfamiliar objects. Medical dolls have also been used to prepare patients
for procedures. Preparing adolescents for painful procedures is as important as preparing younger children. Adolescents, as well as patients of all ages have the potential
to regress during procedures. Much attention is spent on the patient, and the practitioner should also keep in mind that the parents can escalate and add anxiety to a situation or be a source of calm and control for the child.
The primary modality of the child life program incorporates play. Play is reassuring for
children and familiar, which reduces the discomfort and intimidation of the health care
experience.6 Child life provides praise during a procedure and positive reinforcement.
EMERGENCY DEPARTMENT PREPARATION AND PRESEDATION

Presedation, intrasedation, and postsedation assessment are paramount to a successful sedation. Presedation includes a detailed history and physical examination
to aid in the approach for adequate sedation. The clinician must determine whether
analgesia, anxiolysis, or sedation is required or whether a combination will facilitate
success. Clinicians should ask specifically about previous medical history, surgeries
with prior anesthesia, medication allergies, family history, and current use of medications. The physical examination should focus on the airway, respiratory systems, and
cardiovascular systems. Loss of an adequate airway is a serious complication. A primary focus should be on physical constraints that may interfere with endotracheal
intubation to avoid this complication.
The clinician must ask about obstructive airway concerns such as signs of snoring,
stridor, symptomatic asthma, history of heart disease, gastroesophageal reflux, or
swallowing issues. A common approach to obtain important information in emergent
situations is to use the AMPLE approach to obtain a focused history, which is an
acronym for asking specifically about patient allergies, medication use, past medical
history, the patients last meal consumed, and the event or incident that led to the presentation requiring the procedure.
Evidence specific for children regarding identification and management of the difficult airway is limited, but much has been extrapolated from experience with adults,
including the Mallampati classification (Fig. 2). The Mallampati grading system is
used to assess for potential difficult airway. Mallampati scores that are high may
also predict difficult bag-mask ventilation and airway obstruction once musclerelaxing sedative agents are administered. Mallampati I is when the examiner can visualize the tonsillar pillars. Class II is when the uvula alone is visualized. Class III is when
the soft palate is seen, and class IV is when solely the hard palate is visualized. Emergency physicians should be cautious with patients who may have airway challenges
such as Pierre Robin syndrome with micrognathia and trisomy 21 because of the patients large tongues and cervical spine instability. In addition to an appropriate history
and physical examination, patients should be classified according to the American
Society of Anesthesiologists (ASA) Physical Status Classification (Table 1).7 Children
who are in ASA category III or higher may not be candidates for elective procedural

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Fig. 2. Mallampati grading system. Class I (upper left), the examiner can visualize the
tonsillar pillars. Class II (upper right), the uvula alone is visualized. Class III (lower left),
the soft palate is seen. Class IV (lower right), solely the hard palate is visualized.

Table 1
ASA classification: does anesthesia contribute to operative mortality?
ASA I

Healthy patient without systemic disease

ASA II

Patient with mild systemic disease

ASA III

Patient with severe systemic disease

ASA IV

Patient with severe systemic disease posing a threat to life

ASA V

Moribund patient who cannot survive without surgery

Data from Cohen M, Duncan P, Tate R. Does anesthesia contribute to operative mortality? JAMA
1988;260(19):285963.

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sedation in the emergency department. Alternative means to providing safe analgesia

and anesthesia should be explored, but it is common for ASA III patients to have a procedure performed in the emergency department if necessary. The risks and benefits of
performing the procedure in the emergency department must be assessed ahead of
time.
Preparation, preparation, preparation is a mantra in emergency medicine. It is often
an afterthought in the chaotic environment of the emergency department. However,
procedural sedation is often planned and the practitioner is able to have all needed
equipment at the bedside. The mnemonic SOAP ME is useful to remind the practitioner of what may be needed at the bedside: suction, oxygen, and bag-mask apparatus for positive pressure ventilation that is age fitting; appropriately sized airway
equipment (including airway adjuncts such as oropharyngeal/nasopharyngeal airway,
endotracheal tubes, laryngoscope, and blade with functioning light source); pharmaceuticals not only for the procedure, but reversal agents; and monitoring equipment as
well as emergency cart with code medications and defibrillator.
The next consideration should be the childs risk of aspiration (Table 2). In the emergency setting this may be a luxury not afforded to the physician, but it still must be
considered. Most patients who undergo sedation and analgesia are sufficiently
conscious to protect their airways, but the potential to progress to a deeper state of
sedation exists and raises the risk for aspiration. Therefore, it is recommended that
the patient ingest nothing by mouth before any procedure requiring sedation.8 Often
there are institution-specific guidelines with similar restrictions seen and clinicians
should seek out their own institutions guidelines.
Some investigators have argued there to be no correlation between fasting status
and the incidence of aspiration. A large-scale report from The Pediatric Sedation
Research Consortium documented only a single aspiration in 30,037 pediatric sedations outside the operating room. Emesis was only reported in 1 of 200 patients, which
typically was in the recovery phase of the sedation.9 There is weak evidence to support fasting requirements before procedural sedation in the emergent setting; however, The Joint Commission has regarded trivializing nothing-by-mouth status
before PSA to be poor medical practice.
Preferably, 1 physician should be responsible for the sedation while another physician performs the procedure. However, in the community hospital setting this may not
be practical. Monitoring may be performed by an emergency nurse while a single
physician safely and effectively performs the procedure and sedation.10 The emergency physician should understand and be competent in sedation drug pharmacology,

Table 2
Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce
the risk of pulmonary aspiration
Ingested Material

Minimum Fasting Period

Clear liquids

Stop 2 h before procedure

Human milk

Stop 4 h before procedure

Infant formula or nonhuman milk

Stop 6 h before procedure

Light meal (eg, toast and clear liquid)

Stop 6 h before procedure

Adapted from American Society of Anesthesiologists Committee. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration:
application to healthy patients undergoing elective procedures: an updated report by the
American Society of Anesthesiologists Committee on Standards and Practice Parameters. Anesthesiology 2011;114(3):495511.

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anticipate possible complications, and be prepared for necessary resuscitation and recovery of care.
INTRASEDATION

Once the patient has had appropriate presedation evaluation, additional preparation
includes setting up your intrasedation continuous monitoring, which is necessary for
a successful sedation. The degree to which a childs respiratory or cardiovascular
status is continuously monitored is scenario specific. Children who receive simple/
minimal anxiolysis generally do not require any ongoing monitoring beyond initial,
and possibly repeated, vital signs. When continuous monitoring is desired, it should
include pulse oximetry, cardiac, blood pressure, and capnography. Monitoring is
appropriate and recommended for patients who are ASA class II to III and is mandatory for patients in class IV and V.
Capnography is an adjunct that is an important portion of continuous monitoring.
Arterial hypoxia identified with pulse oximetry appears after hypoventilation. Increased
end-tidal carbon dioxide levels have been reported with children receiving respiratory
depressant sedative agents.11 When hypoventilation occurs, capnography provides
an early indication and is an additional tool to assess for potential ventilatory failure.12
Often practitioners place the patient on nasal cannula oxygen, and hypoxia is not
appreciated. Capnography in this setting leads to early detection of apnea because
of the absence of the end-tidal waveform being the earliest sign of airway obstruction.
Continuous capnometry should be considered in patients who are sensitive to both
carbon dioxide tension as well as oxygen saturation, including those with increased
intracranial pressure or certain cardiac lesions.13
SELECTING AN AGENT FOR PSA

When selecting an agent for PSA it is important for the emergency practitioner to
understand the pharmacology of the agent used and to define the goals of the procedure. Procedures are often done that are anxiety provoking, but painless. An example
is the anxiety produced by diagnostic imaging. Some procedures are painful and
solely require analgesia. An example is the nondisplaced fracture that needs to be
splinted and requires little to no manipulation. Then there are procedures that cause
both anxiety and pain and manipulation is required, such as the face laceration repair,
the reduction of a distal radius fracture, or incision and drainage of an abscess. Here
the physician desires an agent that treats pain and anxiety, but may also want an agent
that achieves amnesia. By knowing the pharmacology of each agent, the emergency
practitioner can choose a particular agent with the desired effect, and is able to avoid
particular side effects (Fig. 3). Choosing an agent correctly can help avoid dreaded
complications such as cardiovascular depression and hypotension.
ANALGESIA

Analgesia is best defined as the alleviation of pain without intentionally producing a

sedated state. A change in mental status may be achieved incidentally when analgesic
medications are used. Pain is often undertreated in pediatrics, which is thought to be
secondary to problems quantifying pain in young children.3 There are a variety of
agents that can be helpful to the emergency physician when trying to achieve analgesia with or without an element of sedation.
Infants have physiologic and behavioral responses to pain (ie, increased blood pressure, respiratory rate, and heart rate; crying; flushing; diaphoresis; facial expression;

Pediatric Sedation and Analgesia

Fig. 3. Agents for PSA and their side effects. CT, computed tomography; IN, intranasal; MRI, magnetic resonance imaging; I&D, incision and drainage;
PO, by mouth; US, ultrasound.

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and body movements). However, it is often difficult to quantify pain in infants. For this
reason, researchers have attempted to develop tools for pediatric pain assessment. In
the neonatal intensive care unit there are assessment tools such as the Neonatal Pain
Agitation and Sedation Scale (N-PASS) and the Neonatal Infant Pain Scale (NIPS) that
attempt to identify pain and allow the practitioner to adequately address it in this special population.14 Preschoolers (34 years old) can use the OUCHER scale. This scale
combines both numeric and face scales for young children to point to when describing
their pain.15
The FACES scale requires the child to point to the face that best describes the
pain.16 The FACES scale is reserved for patients 3 to 12 years old. Older children
can be assessed using a visual analog scale. This method has a child 8 to 11 years
old rate the intensity of their pain on a horizontal or numeric scale from 0 to 10.
School-aged or adolescent children are able to perform self-reported numeric pain
rating scales. In this case, pain is rated from 1 to 10. Self-reporting is the ideal measure
to assess pediatric pain when appropriate.17

It is important to keep in mind the desired effect and the age of the patient when
selecting an agent for analgesia. Nonpharmacologic interventions should always be
considered when approaching a child who requires analgesia, or for the completion
of diagnostic or therapeutic procedure, but the practitioner must always ensure that
pain is adequately addressed.
Topical agents including a eutectic mixture of lidocaine and prilocaine (EMLA), lipodermal lidocaine 4% (LMX), and lidocaine/epinephrine/tetracaine (LET) are excellent
options for infants receiving a painful procedure. Also, nonnutritive sucking and highconcentration sucrose solutions have been efficacious. Approximately 1 to 2 mL of
24% to 50% sucrose can be used, typically placed in the cheek with a syringe or pacifier.18 The onset is within 2 minutes. This option is useful up to 6 months of age and can
be effective in term or preterm (<1 month) neonates.19 The mechanism of action is
thought to be release of endogenous endorphins.17 A variety of commercially available
products are available or it can be made up without difficulty.
Topical agents can also be used in older children to pretreat and lessen the pain
of venipuncture, laceration repair, or even for lumbar puncture. The agents that are
commonly used include LET (lidocaine 4%, epinephrine 0.1%, and tetracaine
0.5%).20 LET is most appropriate for small lacerations less than 5 cm to avoid intoxication and excess administration. This agent has been shown to be more effective for
scalp and facial lacerations than for truncal and extremity lacerations. Resch and colleagues21 showed 85% complete anesthesia when repairing uncomplicated face and
scalp lacerations with primary closure. LET is available as an aqueous solution or gel.

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From 1 to 3 mL are applied to an open wound. The onset of action is within 20 to 30 minutes. LET can be toxic to the cardiovascular system and central nervous system (CNS).
A concerning side effect is methemoglobinemia, and LET should be used with caution
on mucous membranes.22 Distal anatomic areas such as the tip of the phalange,
nose, or penis may be contraindicated because of LETs epinephrine component.
LMX-4 is another topical agent available for use. The onset of action is within 30 minutes and the effect can last up to 1 hour. EMLA is another common agent used in the
emergency department. The product contains a eutectic mixture of local anesthetics
(2.5% lidocaine and 2.5% prilocaine) in a cream base. EMLA and LMX-4 can be used
on intact skin and used to prepare for venous or arterial puncture, placement of an
intravenous (IV) catheter and lumbar puncture. EMLA is applied topically in a dose
of 1 g for patients less than 5 kg to 2 g for patients more than 5 kg applied over
10 cm. EMLA takes approximately 1 hour to achieve peak effect, which can last up
to 2 hours even after the cream is removed and has been argued to be the disadvantage of EMLA in the emergency department. EMLA has similar side effects to those
present in other topical agents, including methemoglobinemia.22
Another option to painlessly obtain IV access is needle-free injection of lidocaine
using the J-tip. This system is needle free and is limited to a single use. The device
uses highly pressurized carbon dioxide to push lidocaine through skin and 5 to
8 mm of subcutaneous tissue. The onset of action is 1 to 3 minutes. The needleless
administration of lidocaine into the epidermis is associated with minimal discomfort.
There is not much literature to support its use in preterm infants or neonates. Ferayorni
and colleagues23 showed that needle-free injection of lidocaine administered before
lumbar puncture in infants can offer analgesia.
Other options for noninvasive intervention include intranasal midazolam and fentanyl. Nasal therapy is an effective option because of avoidance of first-pass hepatic
metabolism. There is a fast onset and increased bioavailability with either option.
The mode of delivery is through an atomizer (Fig. 4) added to the end of a syringe.
One study showed that the intranasal route showed faster sedation onset, greater proportion of patients achieving adequate sedation, and higher rate of satisfied parents.
The same study showed that pediatric sedation with buccal or nasal midazolam
aerosol is effective, but not clearly superior to the oral route.24 Even in the best of these
groups, only one-fourth of the children were inadequately sedated. The intranasal
route showed faster sedation onset and a greater proportion of patients receiving
adequate sedation. Intranasal midazolam dripped into the nares had not been well
tolerated because of its acidity and the resulting pain of administration. Intranasal
midazolam is dosed 0.2 to 0.3 mg/kg and has an onset of 10 minutes.25,26 The
dose cannot be lowered because of association of failed sedation and potential for
paradoxic effect.
Other medications that can be administered intranasally include fentanyl and ketamine. Intranasal fentanyl can be given at a dose of 1 to 2 mg/kg and the onset of effect
is at 10 minutes. Intranasal fentanyl is an effective and a safe alternative to IV or intramuscular (IM) morphine for managing acute pain in children presenting to the emergency department. Intranasal fentanyl can decrease IV placement for analgesia by
60% and it reduces the time to analgesia administration by about half.27 Intranasal
ketamine was shown to edge midazolam with success rates approaching 89%.
Combining midazolam did not improve the level of sedation.28
Fentanyl administered via nebulizer is another quick and effective option to achieve
analgesia when vascular access is not available, and is another option to add to the
so-called ouchless emergency department. In a randomized clinical trial by Miner
and colleagues,29 41 patients either received IV fentanyl citrate 1.5 mg/kg or nebulized

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Fig. 4. Atomizer attached to syringe for intranasal administration.

fentanyl 3 mg/kg. The nebulized fentanyl group had similar visual analog scores to the
IV route and appeared to be a feasible and safe alternative (Table 3).
Ibuprofen is a nonsteroidal antiinflammatory medication that is available for use
against mild to moderate pain. Ibuprofen is available for use in children 6 months
old and older. The mechanism of action includes prostaglandin inhibition. The agent
is metabolized by the liver and it is subsequently excreted in the urine. The dose
for pain reduction is 10 mg/kg every 6 to 8 hours with a maximum daily dose of
40 mg/kg.30
The most commonly used agent for pain management in children is acetaminophen.
It is a safe choice for the treatment of pediatric pain. The dose is 15 mg/kg every
4 hours with a maximum dose of 90 mg/kg/d for children.30
Ketorolac is a potent nonsteroidal antiinflammatory agent that is available in both IV,
IM, and oral form. Its effects are most comparable and compatible with ibuprofen. The
medication is strictly contraindicated in renal failure, peptic ulcer disease, allergy to
nonsteroidal antiinflammatory drugs (NSAIDs), bleeding disorder, and platelet
dysfunction. Recommended dosing for children is age dependent. Per the manufacturer recommendations, children between 2 and 16 years old are dosed 0.5 mg/kg
IV with a maximum dose of 15 mg. This group can receive up to 1 mg/kg intramuscularly and a maximum dose of 30 mg. Children older than 16 years or more than 50 kg
can receive 30 mg IV every 6 hours and intramuscularly receive 60 mg for 1 dose. Both
routes have a maximum allowance of 120 mg/d.30
Morphine sulfate is a commonly used opiate medication that has a rapid onset of 4
to 6 minutes. The duration of effect is 2 to 3 hours when given intravenously. The
appropriate dosing is 0.1 to 0.2 mg/kg IV, IM, or subcutaneously.30

Table 3
Profile of analgesia agents
Analgesics

Dose (mg/kg)

Route

Maximum Unit Dose

(mg/kg)

Duration

Precautions

Comments

Morphine

0.10.2

IM/IV/SQ

10

34 h

Histamine release/respiratory
depression

Better absorbed SQ than IM

0.0010.005

IM/IV/IN

0.05

0.51 h

Rigid chest

Decrease dose in infants

0.0010.003

IV

0.05

34 min

Rigid chest

Hydromorphone

0.015

IM/IV

2.5 h

Hydrocodone

0.2

Oral

10

46 h

Combine with acetaminophen

Acetaminophen

15

Oral/rectal

1000

4h

Ibuprofen

10

Oral

40

68 h

Asthma, anticoagulated

Cannot use before age 6 mo

Ketorolac

0.51

IV/IM

1530

46 h

Same as ibuprofen

Not to exceed 48 h of tx

Abbreviations: IM, intramuscular; IN, intranasal; SQ, subcutaneous; tx, treatment.

Data from Tschudy M, Arcara K. The Harriet Lane handbook: a manual for pediatric house officers. 19th edition. Philadelphia: Mosby Elsevier; 2012.

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Fentanyl
Remifentanil

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Fentanyl citrate is 100 times more potent then morphine. It is a useful agent for
PSA because it has a rapid onset within 2 to 3 minutes. However, fentanyl has a
short duration of 30 to 60 minutes. Fentanyl lacks the histamine release side effect
associated with morphine and is preferential for patients with hemodynamic instability. Fentanyl can be given intranasally and has a treatment profile that is comparable with IV morphine sulfate. Dosing of fentanyl is 1 to 2 mg/kg/dose (maximum
50100 mg/dose).30
Remifentanil is a potent ultrashort-acting synthetic opioid analgesic drug. Because
the medication is so short acting, an infusion is often needed to have continuous analgesia. Thus the goal of analgesia for a given procedure must be considered. Typical
dosage is 1 mg/kg given over 30 to 60 seconds followed by an infusion of 0.01 to
2 mg/kg/min. Maximum effect begins within 30 to 90 seconds, and its contextsensitive half-life is less than 5 minutes because it is metabolized by plasma esterases
rather than the liver.
Well-described Adverse Reactions to Opiates

Opiates have common well-described side effects. Adverse reactions seen in children
using opioids include nausea, vomiting, hypotension, respiratory depression, and pruritus caused by histamine release. A well-known and serious side effect of fentanyl is
chest wall rigidity. The treatment of rigid chest syndrome is aggressive respiratory
support, which may require intubation and chemically induced paralysis, and use of
an opioid reversal agent such as naloxone. The dosing for naloxone when needed
for opiate reversal is 0.1 mg/kg, which can be repeated every 2 to 3 minutes.30
DISSOCIATIVE AGENTS
Ketamine

Ketamine is a dissociative anesthetic related to phencyclidine. The mechanism of action is disconnection between the thalamocortical and limbic systems. The end result
is that the patient is moderately sedated and in a state in which amnesia and analgesia
are also accomplished. This dissociative agent is the most commonly used sedative in
the United States. Having both anesthetic and analgesic properties have made the
drug an attractive choice for the emergency physician.11 Therefore, ketamine can
be used for painful procedures while maintaining airway patency and cardiac function.
Prior guidelines strongly urged against the use of ketamine in children between the
ages of 3 and 12 months. A recent meta-analysis showed that the previous concerns
for higher risks of airway compromise are anecdotal.31 The latest absolute contraindications for the use of ketamine include infants less than 3 months old because of a
higher risk of airway compromise. Several studies show an increase in airway obstruction, apnea, and laryngospasm in this age group.31
There is potential for excess secretions with ketamine use, which use to prompt the
prophylactic use of antisialagogues. Atropine and glycopyrrolate as pretreatment adjuncts to ketamine sedation seem to be unnecessary. The rationale was that these
measures would help reduce accumulated secretions in the posterior pharynx and
potentially reduce the incidence of aspiration or other adverse airway events.32 A large
case series of patients showed the safety profile of ketamine when coadministered anticholinergics were omitted and excessive salivation was uncommon.33 With ketamine
use there has been concern for laryngospasm, which is uncommon. Laryngospasm is
typically easily corrected with bag-valve mask ventilation. In a large meta-analysis,
0.3% of children were reported to have this complication. In the same metaanalysis, for 8282 pediatric ketamine sedations, the overall incidence of airway and

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respiratory adverse events was minimal at 3.9%. This study identified the following independent predictors of airway and respiratory events: younger than 2 years, aged
13 years or older, high IV dosing (ie, 2.5 mg/kg or total dose 5 mg/kg), coadministered anticholinergic, and coadministered benzodiazepine.34
Green and colleagues31 clinical practice guideline for emergency department ketamine use suggests that a minimum dissociative dose is achieved with 1.5 mg/kg IV
and 4 to 5 mg/kg IM. Once the dissociative state is achieved, further dosing does
not deepen sedation and the only need for titration is to maintain the dissociative state
over time.31 The IM route seems to cause more vomiting and causes a prolonged
recovery time compared with the IV route.31 The IV route is preferred for longer procedures and especially with the need for repeat dosing. Repeated IV doses can be
achieved with 0.5 to 1.0 mg/kg if needed for prolonged sedation, whereas IM doses
can be achieved with half of a dose or full dose.31 IV ketamine should be given over
30 to 60 seconds to avoid transient respiratory depression.
Well-described Adverse Reactions to Ketamine

Ketamine is commonly used in pediatric emergency medicine. It is useful as a

sedative-analgesic for painful procedures of short duration. Examples of procedures
for which this agent is commonly used include incision and drainage of an abscess,
closed fracture reduction, and wound repair. Negative effects of ketamine include
emetogenesis, increased intracranial pressure, increased ocular pressure, increased
secretions, apnea, and emergence phenomena.35
Ketamine is thought to be emetogenic and lead to feared emergence reactions.
Some studies suggest that ondansetron administered before sedation may significantly reduce the associated nausea and vomiting. An 8% decrease in the rate of
emesis has been achieved by some study groups.31,36 Children receiving ketamine
have low rates of emergence phenomena. They may dream and hallucinate during recovery, but these dreams are rarely frightening.37 No variable predicts ketamineassociated airway complications, which are the most concerning to the emergency
physician and there is no dose relationship for emesis or recovery agitation.38
The contraindication for patients with increased intracranial pressure is a topic of
debate. New evidence suggests that the effect is likely minimal.39 Some argue that
the agent can be used safely in patients with acute traumatic brain injury, but more
research is needed for this proposal and alternative agents should be the first choice
in patients who have traumatic injury, and should definitively be the drug of choice in
hydrocephalus or central nervous system abnormalities.
Laryngospasm is also a known adverse reaction. Should this occur, the practitioner
may use bag-mask ventilation, and apply digital pressure at the superior jaw notch between the ear and the mandible. Other adverse effects from ketamine include tachycardia, hypertension, nystagmus, and muscle rigidity. Its use is contraindicated in
patients with psychosis. Because of ketamines sympathomimetic effects on the cardiovascular system, its use is contraindicated in patients with certain cardiovascular
diseases.
SEDATIVE/HYPNOTIC AGENTS

Sedative/hypnotics are useful for the patient who requires sedation, and in some
cases amnesia, for a stressful or painful procedure. The benzodiazepines are the
most common agents used in this class. Most agents act by modulating gammaaminobutyric acid receptors. One should keep in mind that several of these agents
have no analgesic properties, and they should provide analgesia in the form of an

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opiate or other suitable class of medication to treat pain adequately. Each agent is discussed later with both pros and cons (Table 4 shows details of sedative/hypnotics and
dissociative agents).
Midazolam

Midazolam is a short-acting benzodiazepine with rapid onset of action. The benzodiazepine class is used for its sedative-hypnotic, anxiolytic, and amnestic effects;
they do not have analgesic properties. Several studies assessing the effectiveness
of midazolam have concluded the agent to be safe and effective in children.40
They can be given with opioids for analgesia. Midazolam has also been used with
ketamine to decrease emergence dysphoria. Titrated benzodiazepines seem to
decrease such reactions effectively but not prophylactically.41 An additional advantage of midazolam is that it can be given via multiple routes (ie, IM, intranasal, rectal,
and oral).
Midazolams time to peak effect is 2 to 3 minutes. The duration of action may be up
to 45 minutes to 1 hour by the IV route. The IV and IM dose of midazolam is 0.1 mg/kg.
Oral midazolam can also be used as an anxiolytic for nonpainful procedures. It is best
when administered to a child with an empty stomach. When a child has recently eaten,
its absorption can be erratic. The usual dose is 0.5 mg/kg.30
Well-described Adverse Reactions to Midazolam

Midazolam can be used as a premedication to reduce anxiety surrounding laceration

repair and local anesthetic administration, and before obtaining IV access. Midazolam
has several well-described adverse reactions of which the clinician should be aware.
Major complications with benzodiazepines include respiratory depression and hypotension. Paradoxic reactions that can occur include combativeness, disorientation,
inconsolable crying, agitation, and restlessness. Other side effects noted with midazolam, in decreasing order of frequency, include oxygen desaturation, apnea, hypotension, and hiccups.42,43 With coadministration with opioids there is risk of hypoxia and
apnea that is greater than with either agent used alone. Flumazenil is a benzodiazepine
antagonist that can be used when iatrogenic overdose has occurred or when undesired effects occur. The pediatric dose of flumazenil is 0.01 mg/kg up to a maximum
of 1 mg. The onset of action is 1 to 3 minutes.30
Propofol

Propofol is a sedative-hypnotic often used as a general anesthetic. Propofol is useful

in children because of the short duration of action (shorter than that of ketamine) and
the ability to achieve motionlessness for the patient. These advantages make it an
ideal agent for obtaining diagnostic imaging and quick procedures such as lumbar
puncture, reduction of dislocations, and laceration repair. When given intravenously
there is an immediate effect, and when ceased there is immediate recovery for the patient, which is helpful when attempting quick procedures at the bedside. Another
advantage is that propofol has antiemetic properties. However, compared with
ketamine, propofol provides no analgesia, prompting the use of parenteral, local, or
regional analgesics to be coadministered.
Propofol is dosed 1 mg/kg with repeat dosing at 0.5 mg/kg.30 Propofol reduces
intracranial pressure, making it a potential choice in hemodynamically stable patients
with head trauma.44 Propofol is contraindicated in any patient with a known allergy to
eggs, soy products, or propofol itself.

Table 4
Commonly used sedative agents
Drug

Route

Dose

Onset

Duration

Disadvantages

Anxiolytic

Midazolam

PO, PR, IV,

IM, IN

PO/PR 0.5 mg/kg IV/IM

0.1 mg/kg IN 0.2 mg/kg

PO/PR 2030 min, IV 1 min,

IM 510 min, IN 5 min

14 h

Ativan

PO, IV

0.05

PO 60 min, IV 1530 min

812 h

No analgesia, paradoxic
reaction, respiratory
depression and
hypotension
Prolonged duration of action

Propofol

IV

Seconds

Minutes
(w610 min)

No analgesia, respiratory and

CV depression

Etomidate

IV

Seconds

Methohexital

IV

Seconds

Minutes
(1520 min)
1090 min

Pentobarbital

IV

12 mg/kg
Maximum unit dose (100 mg)
Repeat 0.05 mg/kg
0.10.3 mg/kg
Maximum unit dose (300 mg)
1 mg/kg
Maximum unit dose (100 mg)
25 mg/kg
Maximum unit dose (200 mg)

<1 min

3090 min

No analgesia, myoclonus,
respiratory depression
No analgesia, respiratory and
CV depressant
No analgesia, respiratory and
CV depressant

Dissociative

Ketaminea

IV, IM, PO

IV 12 mg/kg
IM 34 mg/kg
PO 610 mg/kg

IV 12 min, IM 35 min,
PO 30 min

IV 0.51 h,
IM 12 h,
PO 23 h

Increased ICP, intraocular

pressure, emetogenesis,
hypersalivation,
emergence

Combinationsb

Fentanyl 1
midazolam

IV

Fentanyl 12 mg/kg,
midazolam 0.050.1 mg/kg

IV 12 min

13 h

Respiratory depressant
increased with
combination

Ketofol
(ketamine 1
propofol)

IV

Propofol 1 mg/kg, ketamine

0.5 mg/kg

1 min

Propofol
(minutes);
ketamine
1545 min

Dose regimens vary. Modest

advantage profile

Hypnotic/
sedative

Abbreviations: CV, cardiovascular; ICP, intracranial pressure; PO, by mouth; PR, per rectum.
a
Dosing of atropine (0.01 mg/kg, minimum 0.15 mg, maximum 0.5 mg) or glycopyrrolate 0.005 mg/kg maximum 0.25 mg for increased secretions. Unnecessary
as prophylaxis.
b
Decrease dose of each agent. Begin with narcotic and titrate in sedative. Apnea risk proportional to each agent used.11,30,31,46
Data from Tschudy M, Arcara K. The Harriet Lane handbook: a manual for pediatric house officers. 19th edition. Philadelphia: Mosby Elsevier; 2012.

Pediatric Sedation and Analgesia

Class

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Barbiturates

Barbiturates including pentobarbital are beneficial for their short-acting duration,

which makes them ideal for sedation for imaging procedures that may be time
consuming. They are also a more attractive agent used in the setting of intracranial
injury, in which ketamine is contraindicated or its use is in question. When used alone
in the proper dose, adverse reactions are rare. When sedation doses are used, no
analgesia is accomplished when using barbiturates.
Methohexital

Methohexital is an ultrashort-acting barbiturate with an onset of 30 to 60 seconds.

The duration of effect is only 5 to 10 minutes. A study from a 2009 Pediatric Emergency
Care article showed that methohexital was superior to pentobarbital for the purpose of
sedating emergency department patients for head computed tomography (CT).45 The
IV dose is 1 mg/kg.46 For diagnostic imaging (eg, magnetic resonance imaging [MRI]
and CT), rectal administration can be performed. Per rectum dosing is 25 mg/kg, with
a maximum dose of 1 g.
Thiopental

Like methohexital, thiopental is a short-acting drug. The dose is 2.5 to 5 mg/kg given
by the IV route. The maximum unit dose that can be given is 300 mg. Thiopental has a
duration of action of 20 to 60 minutes. Like other barbiturates, a concerning side effect
is respiratory depression. Thiopental can decrease intracranial pressure, making it a
viable option if there is baseline concern for increased intracranial pressure (eg, patients with head injuries). Thiopental also can be given rectally for procedural sedation
in children.
Pentobarbital

Pentobarbital also is commonly used as a sedative during radiologic procedures. The

drug has an onset of action at approximately 3 to 5 minutes with a duration of action of
30 to 45 minutes. Pentobarbital can also be given via the IV, oral, or rectal route. The
rectal route may lead to a delayed onset of sedation up to 45 minutes. The oral, IV, and
rectal dosing recommendation is 2 to 5 mg/kg.
Well-described Adverse Reactions to Propofol and Barbiturates

Propofol side effects include respiratory depression, apnea, and hypotension.44

Negative effects of barbiturates include hypotension, respiratory depression, and
longer recovery times. When proper dosing of barbiturates is achieved, adverse reactions are rare. For methohexital, adverse reactions include oxygen desaturation, hypoventilation, cough, hypersalivation, and hiccups.
Etomidate

Etomidate works at the gamma-aminobutyric acid receptor to produce hypnosis

without analgesia. With etomidate, protective airway reflexes may be significantly
reduced or briefly lost. The hypnotic is typically associated with rapid sequence intubation but also can be used for PSA. Procedures in which immobility is desired, such
as diagnostic imaging, are ideal. The Pediatric Sedation Research Consortium conducted a study to compare the efficacy, sedation duration, and adverse events after
administration of etomidate or pentobarbital for diagnostic CT scans. Etomidate as
given by emergency physicians was more effective and efficient than pentobarbital,
with rare adverse events.47 Another randomized study in the emergency department
compared patients administered either 0.2 mg/kg of etomidate or 0.1 mg/kg of

Pediatric Sedation and Analgesia

midazolam, and induction and recovery times were shorter with etomidate compared
with midazolam.48
For children 10 years and older the recommended dosing is in the range of 0.1 to
0.3 mg/kg.11 Repeat dosing is accomplished at 0.05 mg/kg every 5 minutes to a
maximum total dose of 0.6 mg/kg to achieve the desired effect. The advantage of etomidate is the relative lack of hemodynamic effects compared with other sedating
agents. Etomidate has also shown a useful effect on the CNS by lowering cerebral
metabolism, cerebral blood flow, and intracranial pressure. Etomidate has no analgesic properties. It is best to treat the patients pain with an analgesic such as
morphine or fentanyl before formal sedation.
Well-described Adverse Reactions to Etomidate

Undesired effects with the use of etomidate include respiratory depression or apnea. It is
recommended that it be given with a slow IV push to prevent this unwanted effect. There
has been a concern regarding adrenal suppression, and this is a topic of much debate.
Etomidate may directly inhibit 11b-hydroxylase, which blocks the conversion of 11deoxycortisol to cortisol. Adrenal suppression has occurred with repeated dosing;
therefore, etomidate is not ideal for prolonged procedures and for now should be
avoided in patients at risk for sepsis or serious bacterial illness. Other adverse reactions
include emesis (during and after the procedure) and myoclonus. Some report myoclonus with etomidate use. This reaction must be considered when planning for a painless
diagnostic procedure, but the studies reviewed suggest that its frequency is minimal.
Nitrous Oxide

Given availability, an inhaled nitrous oxideoxygen combination is useful.49 The advantages of nitrous oxide are a quick onset of action, low incidence of complications, and
the rapid return to the patients baseline level of consciousness. In pediatrics, the use
of nitrous oxide is favored even more because it can be administered without inflicting
pain. Disadvantages are that the effects can be unpredictable and depend on a cooperative patient inhaling the agent. Nitrous oxide can provide the effects of amnesia, sedation, anxiolysis, and mild analgesia, making it an attractive choice for mild procedures.
Nitrous oxide can be delivered by a single tank system that has a fixed ratio of 50%
nitrous oxide and 50% oxygen delivery, or varying concentrations with a multiple tank
system. Concentrations of 33% to 70% nitrous oxide delivered by mask have led to
clinically significant alleviation of anxiety and pain in the pediatric population. The
most cited complications include vomiting and respiratory depression, but these are
infrequent and tend to easily resolve once administration is ceased. This method is
ideal for children between the ages of 2 and 5 years, because younger patients
tend to not tolerate the mask apparatus.
A study by Babl and colleagues50 showed that high-concentration continuous-flow
nitrous oxide (70%) was safe in patients aged 1 to 17 years and in children aged 1 to
3 years. Out of 762 patients, 63 patients sustained 70 mild and self-resolving events
(vomiting [5.7%], agitation [1.3%], nausea [0.9%]), and less than 0.1% serious adverse
events such as chest pain or oxygen desaturation. The concerns with nitrous oxide use
have largely focused on the need for a scavenging system and the risk of diversion.
MEDICATION COMBINATIONS
Fentanyl/Midazolam

Fentanyl/midazolam can be less predictable for sedation and analgesia. This combination carries a similar risk of hypotension and respiratory depression to propofol.

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Both ketamine and propofol, with or without adjunct medications, are superior in their
effectiveness and safety profiles.
Ketamine/Propofol

The combination of ketamine and propofol either in separate syringes or in a single

syringe mixed 1:1 (termed ketofol) was described by Andolfatto and colleagues,51
who argued that the benefit was to use drug doses lower than are typically required
for each agent alone. The nausea-inducing and psychic recovery effects of ketamine
are counterbalanced by the sedative and antiemetic effects of propofol. A potential
advantage of ketofol compared with ketamine alone includes shorter recovery time
and a theoretic lower incidence of recovery agitation. It was similarly argued that
the hypotension seen with propofol is counterbalanced by the mild sympathomimetic
properties of ketamine. The combination has been shown to be chemically stable and
physically compatible when mixed in a single syringe.52,53 A potential advantage of
ketofol compared with propofol alone is the allowance for deep sedation with lower
doses of propofol.
A reduction of side effects when using the ketofol combination is arguable.
Andolfatto and colleagues51 failed to find superiority in patients who received ketofol
for emergency department procedural sedation when assessing reduced incidence of
adverse respiratory events compared with propofol alone. This study included 284 patients who were ASA class 1 to 3 status and 14 years or older. The median ages for
both groups that received ketofol versus propofol alone were between 48 and
54 years, respectively.
Shah and colleagues53 specifically studied patients aged 2 to 17 years. Some
patients received an initial IV bolus dose of ketamine 0.5 mg/kg and propofol
0.5 mg/kg, and the other group received solely a dose of 1 mg/kg ketamine. The
ketamine/propofol had modest differences in total sedation time, time to recovery,
adverse events, and satisfaction scores. Median sedation time was 3 minutes less
in the ketamine/propofol group, median recovery time was faster in the ketamine/propofol group by 2 minutes, and there was less vomiting in this group as well (12%).
Satisfaction scores were higher in the ketamine/propofol group.52 The ketamine/propofol group had patients that required greater than 4 doses, whereas the ketamine
group did not need redosing after 3 doses. The clinical significance of the modest
advantages shown in this study is unclear.
Andolfatto and colleagues54 performed an earlier study in patients with a median
age of 13 years. A single-syringe 1:1 mixture of ketamine and propofol (ketofol) with
a median dose of 0.8 mg/kg was highly effective. Shorter recovery times were reported (14 minutes).54 Sharieff and colleagues,55 in a pilot study of 20 patients aged
3 to 17 years, showed a rapid recovery and 38 minutes to discharge suitability. In
this study, 0.5 mg/kg of ketamine followed by 1 mg/kg of propofol were used.
Dexmedetomidine

Dexmedetomidine is a potent selective alpha-2 adrenergic agonist that provides sedation, anxiolysis, and some analgesia without depressing the respiratory drive.56 Its use
in pediatric procedural sedation is new and experience is limited. It may have a role in
painless procedures such as diagnostic imaging. Several studies have suggested its
superiority when used as a sedative for imaging studies.57 The dose for adults per
the packet insert is an initial IV load of 0.5 to 1 mg/kg over 10 minutes followed by
an infusion of 0.5 to 1 mg/kg/h. It has been noted that higher doses are often needed
to achieve sedation in the pediatric population, such as an IV load of 2 to 3 mg/kg
followed by a continuous infusion of 1 to 2 mg/kg per hour. The data that are available

Pediatric Sedation and Analgesia

in pediatrics use a wide range of doses and more studies are needed to confirm a dose
for effect.
Dexmedetomidine can have biphasic effects with initial increase in blood pressure
and a reflex decrease in heart rate. Because of this, it often has to be loaded for a minimum of 10 to 30 minutes, which should be considered in the emergency setting.
Studies comparing propofol and dexmedetomidine found no difference for success
of MRI imaging procedures in pediatric sedation. Propofol had the advantage of
immediate induction, faster recovery times, and faster discharge times.58
Dexmedetomidine can be administered to children via the intranasal or buccal
routes, although no studies exist regarding the use of these routes for pediatric procedural sedation. In dentistry literature, intranasal dosing at 1.5 mg/kg has been shown to
be as effective as oral midazolam and is associated with lower postprocedural pain
scores. Buccal administration of 3 to 4 mg/kg results in moderate sedation without
reported respiratory complications.
DISCHARGE CRITERIA

Discharge criteria following procedural sedation are based on stable serial vital sign
assessments. This assessment is typically performed by a nurse trained in pediatric
advanced life support (PALS) or advanced pediatric life support (APLS) and includes
blood pressure and pulse oximetry. The patient should return to presedation mental
status and preferably tolerate clear liquids.59 If the patient is asleep, the emergency
department staff should easily be able to rouse patients to their presedation mental
status. The patient should be able to sit unaided (except when this is not a baseline
developmental skill).
SUMMARY

Pain and anxiety in the pediatric population have historically been undermanaged.
There is no justification for this. In the emergency department, pain and procedures
are addressed routinely. The emergency physician should be well versed in providing
analgesia and performing procedural sedation. Emergency physicians performing
these procedures need to be in control of the airway, because compromise is the
most serious complication. A broad understanding of the available safe and effective
agents is key. Emergency clinicians should be fully prepared for the sedation and
analgesia route they choose to use.
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